In order to clarify the effects of drought stress training on the quality and drought resistance of Codonopsis pilosula, this study used PEG to simulate drought stress and employed potting with water control for the drought stress training of C. pilosula plants. The polysaccharide content, secondary metabolites, antioxidant system, and photosynthetic pigment system of C. pilosula after drought stress training were analyzed. The results showed that the content of fructans in the root of C. pilosula increased after two rounds of drought stress treatment, and it was significantly higher than that of the control group. The accumulation of fructans in the root of C. pilosula showed an upward trend during the rehydration treatment. The content of lobetyolin and tangshenoside Ⅰ increased after drought stress treatment compared with that of the control group. The rehydration treatment caused first increasing and then decreasing in the content of lobetyolin, while it had no significant effect on the tangshenoside Ⅰcontent. The content of photosynthetic pigments decreased after drought stress treatment, and it gradually increased during the first round of rehydration and the second round of rehydration. Moreover, the increase was faster in the second round of rehydration than in the first round of rehydration. The content of the peroxidation product malondialdehyde(MDA) and the activities of superoxide dismutase(SOD), peroxidase(POD), and catalase(CAT) increased after drought stress treatment compared with those of the control group, and they showed a tendency of decreasing during rehydration. Moreover, the decrease was faster in the second round of rehydration than in the first round of rehydration. When the plants of C. pilosula after drought stress training were again subjected to severe drought stress, the wilting rate decreased significantly, and the biomass increases significantly. This study showed that the drought stress training could promote the accumulation of polysaccharides and secondary metabolites in the root of C. pilosula. When encountering drought stress again, C. pilosula plants could quickly regulate the antioxidant system and delay the decomposition of chlorophyll to respond to drought stress. The findings provide a theoretical basis for the ecological cultivation of C. pilosula in arid and semi-arid areas.
Codonopsis/growth & development* ; Droughts ; Polysaccharides/metabolism* ; Stress, Physiological ; Water/metabolism* ; Antioxidants/metabolism* ; Photosynthesis ; Drought Resistance

Objective The prevalence of drug-resistant Mycobacterium tuberculosis (Mtb) strains is exacerbating the global burden of tuberculosis (TB), highlighting the urgent need for new treatment strategies for TB. Methods The recombinant adenovirus vaccine expressing cyclic di-adenosine monophosphate (c-di-AMP) phosphodiesterase B (CnpB) (rAd-CnpB), was administered to normal mice via mucosal immunization, either alone or in combination with drug therapy, to treat Mtb respiratory infections in mice.Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of antibodies in serum and bronchoalveolar lavage fluid (BALF). Real-time quantitative PCR was performed to assess the transcription levels of cytokines interferon γ(IFN-γ) and interleukin 10(IL-10) in mouse lungs. Flow cytometry was used to determine the proportions of CD4⁺ and CD8⁺ T cell subsets in the lungs and spleens. ELISA was employed to measure the levels of cytokines IFN-γ, IL-2, IL-10, inflammatory factors IL-6, and tumor necrosis factor α (TNF-α) secreted by spleen cells following antigen stimulation. The bacteria loads in the lungs and spleens of Mtb-infected mice were enumerated by plate counting methods. Resluts Intranasal immunization with rAd-CnpB induced high titers of IgG in mouse serum and the production of IgG and IgA in BALF, along with alterations in T lymphocyte subsets in the lungs and spleens. Administration of rAd-CnpB, either alone or in combination with drugs, to Mtb-infected mice significantly increased serum IgG levels as well as IgA and IgG levels in BALF. rAd-CnpB immunization promoted the secretion of CnpB-specific cytokines and inflammatory factors by splenocytes in Mtb-infected mice. However, rAd-CnpB immunotherapy, either alone or combined with drugs, did not significantly affect the bacterial loads in the lungs and spleens of mice with Mtb respiratory infections. Conclusion Mucosal immunization with rAd-CnpB induced significant mucosal, humoral and cellular immune responses in mice, and significantly enhanced CnpB-specific cellular immune responses in Mtb-infected mice.
Animals ; Adenoviridae/immunology* ; Mycobacterium tuberculosis/genetics* ; Mice ; Female ; Phosphoric Diester Hydrolases/genetics* ; Tuberculosis Vaccines/administration & dosage* ; Tuberculosis/prevention & control* ; Mice, Inbred BALB C ; Cytokines ; Lung/microbiology* ; Immunization ; Bronchoalveolar Lavage Fluid/immunology* ; Immunity, Mucosal

Programmed death 1 (PD-1) and its ligand (PD-L1) serve as crucial targets in cancer immunotherapy, and their inhibitors have significantly improved the prognosis of many patients with malignant tumors. However, the issues of drug resistance and limited overall response rate associated with monotherapy remain prevalent. As a new generation of immune checkpoints, lymphocyte activation gene 3 (LAG-3) synergistically enhances the suppression of T cells alongside PD-1 in various cancers. Combining the blockade of both PD-1 and LAG-3 yields stronger anti-tumor immune effects compared to blocking either target alone, thereby reversing the immunosuppressive state of the tumor microenvironment and reducing the occurrence of resistance. This review covers the structural characteristics of LAG-3 and unveils its specific interactions with PD-1 across multiple cancers, providing a novel reference for overcoming the limitations of single-agent therapy.
Humans ; Neoplasms/immunology* ; Immunotherapy/methods* ; Programmed Cell Death 1 Receptor/metabolism* ; Lymphocyte Activation Gene 3 Protein ; Antigens, CD/metabolism* ; Animals ; Tumor Microenvironment/immunology* ; Immune Checkpoint Inhibitors/therapeutic use*

Objective To investigate the effects of cucurbitacin B (CucB) on alleviating skin lesions and inflammation in psoriasis mice via the cGAS-STING signaling pathway. Methods The expression of genes associated with the cGAS-STING signaling pathway in psoriatic lesions and non-lesional skin was analyzed, and hallmark gene set enrichment analysis was performed. The cytotoxicity of CucB on BMDMs was evaluated using the CCK-8 assay. The expression levels of genes and proteins related to the cGAS-STING signaling pathway, along with the secretion of inflammatory cytokines, were measured at different concentrations of CucB using quantitative PCR, Western blotting, and ELISA. Imiquimod-induced psoriasis BALB/c mice were divided into four groups: normal group, model group, low-dose CucB group [0.1 mg/ (kg.d)], and high-dose CucB group [0.4 mg/ (kg.d)], with five mice per group. PASI scoring was performed to assess the severity of psoriasis after 6 days of treatment, and HE staining was conducted to observe pathological damage. Meanwhile, the mRNA levels of inflammatory cytokines and their secretion were detected by qPCR and ELISA. Results Most cGAS-STING signaling-related genes were upregulated in lesional skin of psoriasis patients, and the hallmark gene set enrichment analysis revealed that the most significantly upregulated genes were primarily associated with immune response signaling pathways. CucB inhibited dsDNA-induced phosphorylation of interferon regulatory factor 3 (IRF3) and STING proteins in both bone-marrow derived macrophages(BMDMs) and THP-1 cells. CucB also suppressed dsDNA-induced mRNA expression of IFNB1, TNF, IFIT1, CXCL10, ISG15, and reduced the secretion of cytokines such as IFN-β, IL-1β, and TNF-α in THP-1 cells. In the imiquimod-induced psoriasis mouse model, CucB treatment reduced psoriatic symptoms, alleviated skin lesions, and attenuated inflammation. ELISA and qPCR results showed that CucB significantly reduced serum secretion levels of IL-6, TNF-α, and IL-1β, as well as the mRNA levels of IL23A, IL1B, IL6, TNF, and IFNB1. Conclusion CucB inhibits cytoplasmic DNA-induced activationc of the GAS-STING pathway. CucB significantly attenuates skin lesions and inflammation in IMQ-induced psoriatic mice, and the potential molecular mechanism may be related to the down-regulation of the cGAS-STING pathway.
Animals ; Psoriasis/pathology* ; Signal Transduction/drug effects* ; Membrane Proteins/genetics* ; Mice ; Nucleotidyltransferases/genetics* ; Disease Models, Animal ; Mice, Inbred BALB C ; Skin/metabolism* ; Triterpenes/therapeutic use* ; Humans ; Cytokines/metabolism* ; Inflammation/drug therapy* ; Male

Rheumatoid arthritis (RA) is an autoimmune disease characterized by complex pathogenesis, with its development closely linked to immune dysregulation. Regulatory T cells (Tregs), as specialized immunomodulatory cells, play a pivotal role in negatively regulating immune responses and maintaining autoimmune tolerance. In recent years, extensive research has focused on the relationship between Tregs and RA pathogenesis, with the functional role of CD8⁺ Tregs as a critical area of investigation. This review summarizes the alterations in CD8⁺ Tregs during RA progression and their potential mechanisms of action. By elucidating the diversity of CD8⁺ Treg subsets and their intricate roles in modulating immune responses, this analysis provides novel insights and therapeutic strategies for RA diagnosis and treatment.
Arthritis, Rheumatoid/pathology* ; Humans ; T-Lymphocytes, Regulatory/immunology* ; CD8-Positive T-Lymphocytes/immunology* ; Animals

Trauma is the main cause of death and disability. Patients with severe trauma have hemorrhagic shock, traumatic coagulopathy and other diseases, which increase the risk of death. Platelets are important in the hemostatic response, but their function is rapidly dysregulated in trauma patients, leading to traumatic coagulopathy, blood loss, and early death. In addition to their role in hemostasis, platelets act as coordinators of the initial immune response, which can lead to immunothrombosis, organ dysfunction, and increased late mortality. At present, the treatment of post traumatic platelet dysfunction is mainly based on early hemostasis, and late prevention and treatment of thrombosis and organ dysfunction. In this review, the characteristics, underlying mechanisms, diagnosis and treatment strategies of platelet dysfunction in different periods are summarized, to provide ideas for studying the mechanism of platelet dysfunction after trauma and the treatment strategy for trauma patients.
Humans ; Wounds and Injuries/therapy* ; Blood Platelets/metabolism* ; Blood Platelet Disorders/etiology* ; Animals ; Hemostasis

OBJECTIVE: To illustrate the role of dehydrocorydaline (DHC) in chronic constriction injury (CCI)-induced neuropathic pain and the underlying mechanism. METHODS: C57BL/6J mice were randomly divided into 3 groups by using a random number table, including sham group (sham operation), CCI group [intrathecal injection of 10% dimethyl sulfoxide (DMSO)], and CCI+DHC group (intrathecal injection of DHC), 8 mice in each group. A CCI mouse model was conducted to induce neuropathic pain through ligating the right common sciatic nerve. On day 14 after CCI modeling or sham operation, mice were intrathecal injected with 5 µL of 10% DMSO or 10 mg/kg DHC (5 µL) into the 5th to 6th lumbar intervertebral space (L5-L6). Pregnant ICR mice were sacrificed for isolating primary spinal neurons on day 14 of embryo development for in vitro experiment. Pain behaviors were evaluated by measuring the paw withdrawal mechanical threshold (PWMT) of mice. Immunofluorescence was used to observe the activation of astrocytes and microglia in mouse spinal cord. Protein expressions of inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), phosphorylation of N-methyl-D-aspartate receptor subunit 2B (p-NR2B), and NR2B in the spinal cord or primary spinal neurons were detected by Western blot. RESULTS: In CCI-induced neuropathic pain model, mice presented significantly decreased PWMT, activation of glial cells, overexpressions of iNOS, TNF-α, IL-6, and higher p-NR2B/NR2B ratio in the spinal cord (P<0.05 or P<0.01), which were all reversed by a single intrathecal injection of DHC (P<0.05 or P<0.01). The p-NR2B/NR2B ratio in primary spinal neurons were also inhibited after DHC treatment (P<0.05). CONCLUSION An intrathecal injection of DHC relieved CCI-induced neuropathic pain in mice by inhibiting the neuroinflammation and neuron hyperactivity.
Animals ; Neuralgia/etiology* ; Mice, Inbred C57BL ; Analgesics/pharmacology* ; Neuroinflammatory Diseases/pathology* ; Constriction ; Male ; Receptors, N-Methyl-D-Aspartate/metabolism* ; Nitric Oxide Synthase Type II/metabolism* ; Mice, Inbred ICR ; Microglia/pathology* ; Spinal Cord/drug effects* ; Female ; Mice ; Tumor Necrosis Factor-alpha/metabolism* ; Disease Models, Animal ; Constriction, Pathologic/complications* ; Interleukin-6/metabolism* ; Astrocytes/metabolism* ; Chronic Disease ; Neurons/metabolism*

Objective To investigate the changes of sex hormones,anti-Müllerian hormone(AMH)level and ovarian ultrasound imaging parameters in women of childbearing age,so as to analyze their predictive value for premature ovarian insufficiency(POI)and establish the predictive model.Methods A total of 1 968 women of childbearing age in The First Affiliated Hospital of Xi'an Jiaotong University from 2018 to June 2022 were selected as research subjects.Their sex hormones and AMH levels were detected,and ultrasonographic features of the ovary were detected,including antral follicle count(AFC),ovarian volume,ovarian cortical volume,ovarian medulla volume,the total area,ovarian cortical area,and ovarian medulla area.The changes in ovarian function status at different age were analyzed,and their predictive value for POI was explored.AMH combined with ovarian ultrasound imaging parameters was used to establish a model for predicting POI.Results Among the 1 968 subjects,the prevalence rate of POI was 3.10％.The prevalence rate of POI was significantly higher in 30-39 years old group than in 20-29 years old group(P＜0.05).The serum AMH level in 30-34 years old group was significantly lower than that in 20-24 years old group and 25-29 years old group(P＜0.05),and the serum follicle stimulating hormone(FSH)and luteinizing hormone(LH)levels were significantly higher in 35-39 years old group than in 30-34 years old group(P＜0.05).The serum estradiol(E2)and AMH levels,AFC,ovarian volume,ovarian cortical volume,ovarian area,and ovarian cortical area were significantly lower than those in the 30-34 years old group(P＜0.05).The serum FSH and LH levels in POI group were significantly higher than women of the same age with normal ovarian function(P＜0.05),while the serum E2 and AMH levels were significantly lower than women of the same age with normal ovarian function(P＜0.05).The AFC,ovarian volume,ovarian cortical volume,ovarian medullary volume,ovarian area,ovarian cortical area,and ovarian medullary area in POI group were significantly lower than women of the same age with normal ovarian function(P＜0.05).The analysis results of the predictive value of hormone indicators for POI showed that AMH had the highest predictive value(AUC=0.957),followed by E2(AUC=0.840).Among the ultrasound imaging indicators,AFC had the largest predictive value(AUC=0.867),followed by ovarian cortical volume(AUC=0.835).The model established by AMH combined with ovarian ultrasound imaging parameters had a good predictive value for POI,and its sensitivity was 94.86％,specificity was 91.23％,AUC was 0.960,and the cutoff value was 12 points.Conclusion The prevalence of POI is high in women aged 30-39 years of reproductive age.The model established by AMH combined with ovarian ultrasound imaging parameters has certain predictive value for POI,especially for women in the occult stage,and thus deserves clinical attention.

Objective To investigate the characteristics of menopause-related symptoms and cognition status of menopausal hormone therapy(MHT)among menopausal women.Methods A total of 619 menopausal women with menopause-related symptoms who were admitted to The First Affiliated Hospital of Xi'an Jiaotong University were selected as the study subjects.Data were collected by questionnaire to analyze the characteristics of menopause-related symptoms,and the menopausal women's cognitive status of MHT and therapeutic effects were explored.Results Among 371 perimenopausal women,the menopause-related symptoms with the top three rates were fatigue(69.81％),insomnia(66.85％),and hot flush-sweating(58.22％).Among 248 postmenopausal women,the menopause-related symptoms with the top three rates were hot flashes and sweating(64.11％),bone and joint pain(60.89％),and fatigue(56.85％).The incidence of insomnia and fatigue in postmenopausal women was significantly lower than that in perimenopausal women(P＜0.01),while the incidence of bone and arthralgia,urinary system infection,vaginal dryness and painful intercourse was significantly higher than that in perimenopausal women(P＜0.01).There was no significant difference in Kupperman score between perimenopausal and postmenopausal women(P＞0.05),but score degree distribution differed significantly(P＜0.05).Perimenopausal women had the highest proportion of mild score while postmenopausal women had the highest proportion of moderate score.There were significant differences in Kupperman score among postmenopausal women with different menopause ages,menopause years and menopause mode(P＜0.05).The earlier menopause age and shorter menopause years,the higher Kupperman score was;the Kupperman score was significantly higher in surgical menopause than in natural menopause(P＜0.05).Multivariate Logistic regression analysis showed that age of 45-54 years old,retirement or unemployment,spouse's disease or death,abnormal sexual life,and high education level were the risk factors for the occurrence of menopausal symptoms(P＜0.05);high family income and＞3 times/week exercise were the protective factors for the occurrence of menopausal symptoms(P＜0.05).The Internet was the way that accounted for the highest proportion of menopausal women's understanding of MHT(39.92％),and the tumor accounted for the highest proportion of menopausal women's concern about MHT(33.67％).There were 465 menopausal women without MHT contraindications(89.77％)who used MHT under the guidance of professional doctors,and their symptoms improved significantly after treatment(P＜0.05).Conclusion Menopausal women have obvious menopause-related symptoms,and the earlier the age,the shorter the menopause years and the more severe symptoms in the surgical menopause.Therefore,it is necessary to pay attention to the impact of menopause on the health of menopausal women and increase the use rate of MHT to improve the quality of life of menopausal women.

Objective:To investigate the possible pathogenesis and possible risk factors of tinnitus related to female menopause.Methods:From April 2016 to October 2016, 59 female patients with menopausal syndrome were diagnosed in the menopause comprehensive management clinic. Tinnitus and menopause questionnaires were conducted, based on whether having tinnitus, those patients were divided into two groups: tinnitus group and no tinnitus group. Age, body mass index (BMI), Kupperman menopausal index (KMI) score, follicle-stimulating hormone (FSH) level of patients in the two groups were analyzed. Menopausal symptoms, related medical history and possible related factors of tinnitus were statistically analyzed.Results:A total of 59 cases were collected, 22 of which were accompanied by tinnitus. The incidence of idiopathic tinnitus was 35.1% (20/57) because 2 cases of thyroid related tinnitus with clear etiology were removed. Complete data were obtained from 17 of 20 patients with idiopathic tinnitus and 26 of 37 patients without tinnitus. Age, BMI, menopause KMI score, hormone level, menopause symptoms and possible factors related to tinnitus were statistically analyzed between the two groups, and the incidence of headache was statistically different between the two groups ( χ2=9.098, P=0.003), but no other factors were statistically significant( P>0.05). The severity of insomnia and tinnitus were further analyzed ( χ2=2.841, P=0.417), and there was no significant difference between the two groups. Conclusion:Headache history may be one of the high risk factors for the occurrence of menopausal tinnitus.